DiGiovanna J J, Gross E G, McClean S W, Ruddel M E, Gantt G, Peck G L
J Invest Dermatol. 1984 Jun;82(6):636-40. doi: 10.1111/1523-1747.ep12261476.
Since etretinate, an aromatic retinoid useful in the treatment of psoriasis and other skin disorders is lipid-soluble, it may be poorly absorbed in the absence of a fat load. We therefore studied serum concentrations of etretinate and its major metabolite (Ro 10-1670) after the controlled administration of etretinate. After an overnight fast, 6 Darier's disease and 4 psoriatic patients received a 1 mg/kg morning dose of etretinate with water or 1 pint of whole milk (fat load). There was a 260% increase (p less than 0.0005) in the mean of each patient's increase in the baseline-corrected peak serum concentration of etretinate after administration with milk (115 +/- 15 micrograms/dl) compared to after administration with water (32 +/- 4 micrograms/dl). Over a 24-h period there was an overall 296 +/- 26% (p less than 0.0005) increase in serum etretinate after administration with milk compared to water in 5 patients with Darier's disease. In contrast to the serum etretinate, there was a 17% mean decrease (p less than 0.025) in the corrected peak serum concentration of Ro 10-1670 in all 10 patients after administration of etretinate with milk compared to water. The net result of these alterations is that the mean corrected serum concentration of etretinate is higher than Ro 10-1670 at all time points measured after milk administration. In contrast, after administration of etretinate with water the major retinoid in the serum is Ro 10-1670. Establishing the clinical significance of these alterations may require controlled clinical trials.
阿维A酯是一种用于治疗牛皮癣和其他皮肤病的芳香维甲酸,由于其脂溶性,在没有脂肪负荷的情况下可能吸收不佳。因此,我们研究了阿维A酯及其主要代谢产物(Ro 10-1670)在阿维A酯控释给药后的血清浓度。经过一夜禁食后,6名 Darier病患者和4名银屑病患者于早晨接受1 mg/kg阿维A酯剂量,用水或1品脱全脂牛奶(脂肪负荷)送服。与用水送服(32±4微克/分升)相比,用牛奶送服后,每位患者阿维A酯基线校正后血清峰值浓度的平均增加值提高了260%(p<0.0005)(115±15微克/分升)。在24小时内,5名 Darier病患者用牛奶送服后血清阿维A酯的总体增加值比用水送服高296±26%(p<0.0005)。与血清阿维A酯相反,在所有10名患者中,用牛奶送服阿维A酯后,Ro 10-1670校正后血清峰值浓度平均下降了17%(p<0.025)。这些变化的最终结果是,在用牛奶送服后测量的所有时间点,阿维A酯校正后血清平均浓度均高于Ro 10-1670。相反,用水送服阿维A酯后,血清中的主要维甲酸是Ro 10-1670。确定这些变化的临床意义可能需要进行对照临床试验。